GFRA2 (GDNF family receptor alpha 2)

Gene

• Entrez ID: 2675
• Gene name: GDNF family receptor alpha 2
• Gene symbol: GFRA2
• Synonyms (NCBI Gene): GDNFRB, NRTNR-ALPHA, NTNRA, RETL2, TRNR2
• Chromosome: 8
• Chromosome location: 8p21.3
• Summary: Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) are two structurally related, potent neurotrophic factors that play key roles in the control of neuron survival and differentiation. The protein encoded by this gene is a member of the

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs796065050	G>A	Drug-response	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1017581	hsa-miR-1253	CLIP-seq
MIRT1017582	hsa-miR-1260	CLIP-seq
MIRT1017583	hsa-miR-1260b	CLIP-seq
MIRT1017584	hsa-miR-188-3p	CLIP-seq
MIRT1017585	hsa-miR-3150b-3p	CLIP-seq
MIRT1017586	hsa-miR-3156-3p	CLIP-seq
MIRT1017587	hsa-miR-3192	CLIP-seq
MIRT1017588	hsa-miR-345	CLIP-seq
MIRT1017589	hsa-miR-3591-3p	CLIP-seq
MIRT1017590	hsa-miR-3609	CLIP-seq
MIRT1017591	hsa-miR-3689a-3p	CLIP-seq
MIRT1017592	hsa-miR-3689c	CLIP-seq
MIRT1017593	hsa-miR-4256	CLIP-seq
MIRT1017594	hsa-miR-4728-5p	CLIP-seq
MIRT1017595	hsa-miR-4733-3p	CLIP-seq
MIRT1017596	hsa-miR-4768-3p	CLIP-seq
MIRT1017597	hsa-miR-4778-5p	CLIP-seq
MIRT1017598	hsa-miR-4784	CLIP-seq
MIRT1017599	hsa-miR-490-3p	CLIP-seq
MIRT1017600	hsa-miR-548ah	CLIP-seq
MIRT1017601	hsa-miR-665	CLIP-seq
MIRT1017602	hsa-miR-765	CLIP-seq
MIRT1017603	hsa-miR-1202	CLIP-seq
MIRT1017604	hsa-miR-155	CLIP-seq
MIRT1017605	hsa-miR-2355-5p	CLIP-seq
MIRT1017606	hsa-miR-3194-5p	CLIP-seq
MIRT1017607	hsa-miR-361-3p	CLIP-seq
MIRT1017608	hsa-miR-3621	CLIP-seq
MIRT1017609	hsa-miR-365	CLIP-seq
MIRT1017610	hsa-miR-3943	CLIP-seq
MIRT1017611	hsa-miR-3972	CLIP-seq
MIRT1017612	hsa-miR-4727-5p	CLIP-seq
MIRT1017613	hsa-miR-4769-3p	CLIP-seq
MIRT1017582	hsa-miR-1260	CLIP-seq
MIRT1017583	hsa-miR-1260b	CLIP-seq
MIRT1017584	hsa-miR-188-3p	CLIP-seq
MIRT1017586	hsa-miR-3156-3p	CLIP-seq
MIRT1017588	hsa-miR-345	CLIP-seq
MIRT1017593	hsa-miR-4256	CLIP-seq
MIRT1017597	hsa-miR-4778-5p	CLIP-seq
MIRT1017607	hsa-miR-361-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005886	Component	Plasma membrane	IDA	9576965
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0007169	Process	Cell surface receptor protein tyrosine kinase signaling pathway	IEA
GO:0007169	Process	Cell surface receptor protein tyrosine kinase signaling pathway	TAS	9192898
GO:0007399	Process	Nervous system development	IBA
GO:0007399	Process	Nervous system development	IEA
GO:0009897	Component	External side of plasma membrane	IBA
GO:0016020	Component	Membrane	IEA
GO:0016167	Function	Glial cell-derived neurotrophic factor receptor activity	IBA
GO:0016167	Function	Glial cell-derived neurotrophic factor receptor activity	IDA	29414779, 31535977
GO:0016167	Function	Glial cell-derived neurotrophic factor receptor activity	IEA
GO:0016167	Function	Glial cell-derived neurotrophic factor receptor activity	TAS	10829012
GO:0019898	Component	Extrinsic component of membrane	TAS	10829012
GO:0035860	Process	Glial cell-derived neurotrophic factor receptor signaling pathway	IDA	29414779, 31535977
GO:0038023	Function	Signaling receptor activity	IEA
GO:0043235	Component	Receptor complex	IBA
GO:0098552	Component	Side of membrane	IEA
GO:1904399	Function	Heparan sulfate binding	IDA	29414779

Other IDs

• MIM: 601956
• HGNC: 4244
• e!Ensembl: ENSG00000168546

Protein

• UniProt ID: O00451
• Protein name: GDNF family receptor alpha-2 (GDNF receptor alpha-2) (GDNFR-alpha-2) (GFR-alpha-2) (GDNF receptor beta) (GDNFR-beta) (Neurturin receptor alpha) (NRTNR-alpha) (NTNR-alpha) (RET ligand 2) (TGF-beta-related neurotrophic factor receptor 2)
• Protein function: Receptor for neurturin (NRTN), a growth factor that supports the survival of sympathetic neurons (PubMed:10829012, PubMed:29414779, PubMed:31535977, PubMed:9182803). NRTN-binding leads to autophosphorylation and activation of the RET receptor (P
• PDB: 5MR4, 5MR5, 6GL7, 6Q2O, 6Q2R
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02351	GDNF	40 → 114	GDNF/GAS1 domain	Domain
  PF02351	GDNF	161 → 241	GDNF/GAS1 domain	Domain
  PF02351	GDNF	251 → 347	GDNF/GAS1 domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: [Isoform 1]: found in both brain and placenta. {ECO:0000269|PubMed:9259272}.
• Sequence:

  MILANVFCLFFFLDETLRSLASPSSLQGPELHGWRPPVDCVRANELCAAESNCSSRYRTL
  RQCLAGRDRNTMLANKECQAALEVLQESPLYDCRCKRGMKKELQCLQIYWSIHLGLTEGE
  EFYEASPYEPVTSRLSDIFRLASIFSGTGADPVVSAKSNHCLDAAKACNLNDNCKKLRSS
  YISICNREISPTERCNRRKCHKALRQFFDRVPSEYTYRMLFCSCQDQACAERRRQTILPS
  CSYEDKEKPNCLDLRGVCRTDHLCRSRLADFHANCRASYQTVTSCPADNYQACLGSYAGM
  IGFDMTPNYVDSSPTGIVVSPWCSCRGSGNMEEECEKFLRDFTENPCLRNAIQAFGNGTD
  VNVSPKGPSFQATQAPRVEKTPSLPDDLSDSTSLGTSVITTCTSVQEQGLKANNSKELSM
  CFTELTTNIIPGSNKVIKPNSGPSRARPSAALTVLSVLMLKLAL

• Sequence length: 464

Pathways

Reactome:

RAF/MAP kinase cascade
RET signaling

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ASTHMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLOR VISION DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEMENTIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FRONTOTEMPORAL DEMENTIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG ADENOCARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NON-SMALL CELL LUNG CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pazopanib response	drug response	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PELVIC ORGAN PROLAPSE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SQUAMOUS CELL CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
STEVENS-JOHNSON SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TOXIC EPIDERMAL NECROLYSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenoma	Adenoma	BEFREE	24402129		★☆☆☆☆ Found in Text Mining only
Bipolar Disorder	Bipolar Disorder	GWASCAT_DG	26806518		★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	24402129, 35114976	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	25707620	Associate	★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular disease	Pubtator	35736394	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	30811036		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	35114976	Associate	★☆☆☆☆ Found in Text Mining only
Epiretinal Membrane	Epiretinal Membrane	BEFREE	12032115		★☆☆☆☆ Found in Text Mining only
Frontotemporal dementia	Frontotemporal dementia	GWASCAT_DG	29724592		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Frontotemporal Lobar Degeneration	Frontotemporal dementia	BEFREE	29724592		★☆☆☆☆ Found in Text Mining only
Heart Failure	Heart failure	Pubtator	35736394	Associate	★☆☆☆☆ Found in Text Mining only
Hepatitis C	Hepatitis c	Pubtator	25707620	Associate	★☆☆☆☆ Found in Text Mining only
Hirschsprung Disease	Hirschsprung Disease	BEFREE	11409869		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	25707620		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	24067900, 27400681		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	27400681, 30722993		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	BEFREE	30722993		★☆☆☆☆ Found in Text Mining only
Neuropathy	Neuropathy	BEFREE	24067900		★☆☆☆☆ Found in Text Mining only
Pancreatic carcinoma	Pancreatic carcinoma	BEFREE	24067900, 27400681		★☆☆☆☆ Found in Text Mining only
PIGMENTARY DISORDER, RETICULATE, WITH SYSTEMIC MANIFESTATIONS	Pigmentary Disorder, Reticulate, With Systemic Manifestations	BEFREE	12032115		★☆☆☆☆ Found in Text Mining only
Pituitary Neoplasms	Pituitary neoplasm	Pubtator	24402129	Associate	★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	20116071, 20369355		★★☆☆☆ Found in Text Mining + Unknown/Other Associations